We report on a 60 yrs. patient with short stature (< 2nd centile), spontaneous eruption of 7 teeth only, fusion of C1 to C4 vertebrae with partial occipito-atlantal fusion. Two of her seven siblings presented oligodontia. Standard chromosome analysis in the proband showed a mosaic karyotype 45,X[3]/46,XX[27], which may relate with the short stature. Array-CGH (60K, Agilent Technologies) showed a ∼1 Mb duplication encompassing chromosome 7p spanning eight genes (ISPD, SOSTDC1, LRRC72, ANKMY, TSPAN13, AGR2 and AGR3): (arr[hg19]7p21.2p21.1(15,926,980x2,15,994,233-17,074,396x3,17,222,770x2). Real-time PCR on available members showed the duplication segregated in the two siblings with oligodontia, but it was absent in one healthy sister. We hypothesize that oligodontia is associated with the duplication of SOSTDC1(OMIM* 609675), which is a member of the sclerostin family. The protein acts as a bone morphogenetic protein (BMP) antagonist. Mice overexpressing Sostdc1 have a reduced number of teeth, whereas Sostdc1 -/-show an increased number of teeth number and anomalies in teeth morphology. The gene has been demonstrated to antagonize Wnt signaling in mice. Interestingly, WNT10Amutations have been associated with oligodontia in humans. In conclusion, we speculate that the duplication of SOSTDC1 at chromosome 7p21.2p21.1 may increase its protein level leading to oligodontia in our family. SOSTDC1 could be a new candidate gene to be screened in isolated oligodontia.
Oligodontia segregating with a 7p21.2p21.1 ∼ Mb duplication in an Italian family with three affected siblings
DI GREGORIO, ELEONORA;TALARICO, FRANCESCA;BRUSCO, Alfredo;BRACCO, CECILIA
2014-01-01
Abstract
We report on a 60 yrs. patient with short stature (< 2nd centile), spontaneous eruption of 7 teeth only, fusion of C1 to C4 vertebrae with partial occipito-atlantal fusion. Two of her seven siblings presented oligodontia. Standard chromosome analysis in the proband showed a mosaic karyotype 45,X[3]/46,XX[27], which may relate with the short stature. Array-CGH (60K, Agilent Technologies) showed a ∼1 Mb duplication encompassing chromosome 7p spanning eight genes (ISPD, SOSTDC1, LRRC72, ANKMY, TSPAN13, AGR2 and AGR3): (arr[hg19]7p21.2p21.1(15,926,980x2,15,994,233-17,074,396x3,17,222,770x2). Real-time PCR on available members showed the duplication segregated in the two siblings with oligodontia, but it was absent in one healthy sister. We hypothesize that oligodontia is associated with the duplication of SOSTDC1(OMIM* 609675), which is a member of the sclerostin family. The protein acts as a bone morphogenetic protein (BMP) antagonist. Mice overexpressing Sostdc1 have a reduced number of teeth, whereas Sostdc1 -/-show an increased number of teeth number and anomalies in teeth morphology. The gene has been demonstrated to antagonize Wnt signaling in mice. Interestingly, WNT10Amutations have been associated with oligodontia in humans. In conclusion, we speculate that the duplication of SOSTDC1 at chromosome 7p21.2p21.1 may increase its protein level leading to oligodontia in our family. SOSTDC1 could be a new candidate gene to be screened in isolated oligodontia.
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